Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: A randomized controlled trial

Abstract

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with Free

Hepatoprotective properties of extensively studied medicinal plant active constituents: Possible common mechanisms

“…A preparation with the name of Realsil (RA) which comprises the silybin phytosome complex (silybin plus phosphatidylcholine) co-formulated with vitamin E was tested. Treatment for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight (Loguercio et al, 2012).…”

“…Silibinin was also reported to improve hepatic oxidative stress and inflammation through the c-Jun NH2-terminal kinase (Salamone et al, 2012a) and nuclear factor kappa B (NF-kB) (Salamone et al, 2012b) pathways. In a clinical trial, silibinin given for 12 months in combination with vitamin E and phosphatidylcholine improved hepatic enzymes and insulin resistance in NAFLD patients (Loguercio et al, 2012). The anti-inflammatory, immunemodulating activity, antifibrotic, and antioxidant effects of silymarin that contribute to its hepatoprotective effect are summarized in a review by Abenavoli et al (2010).…”

Oxidative stress: New insights on the association of non-alcoholic fatty liver disease and atherosclerosis

“…Moreover, some studies showed a positive effect of silybin on fibrosis and oxidation [116,117] . In a recent large multicenter RCT, a combination of silybin, vitamin E and phosphatidylcholine reduced hepatic damage and IR [118] . L-carnitine, an endogenous substance precursor of carnitine-palmitoyltransferase 1, is involved in the mitochondrial β-oxidation that affects mitochondrial function.…”

Flavonoids and Related Compounds in Non-Alcoholic Fatty Liver Disease Therapy

“…Combination of silibinin with phospholipids appears to increase its bioavailability [101]. Several clinical studies evidence the efficacy of silibinin combined with phospholipids and vitamin E in patients with NAFLD, who exhibit improvements in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transferase (γGT) levels, insulin resistance and liver histology in addition to the normalization of the cholestasis and cholesterol levels [102][103][104][105].…”